title: Association of hypoxia-inducible factor-1 expression with histology in epithelial ovarian tumors: a quantitative analysis of HIF-1.
abstract: BACKGROUND
  Hypoxia-inducible factor-1 (HIF-1) is an essential transcription factor that mediates cellular and systemic homeostatic responses to reduced oxygen availability in mammals. So far, using immunohistochemistry we have analyzed the association of HIF-1alpha expression with histological type among epithelial ovarian tumors. In the present study, quantitative analyses of activated HIF-1 level in the nucleus and of accumulated HIF-1alpha level in the cytoplasm were performed to clarify whether or not the hypoxic state would be correlated to histology, malignancy, and tumor size in epithelial ovarian tumors.
  
  
  METHODS
  HIF-1 level in the nucleus was analyzed using DNA binding assay, and HIF-1alpha level in the cytoplasm was measured by ELISA for a total of 36 epithelial ovarian tumors as follows: 5 serous adenocarcinomas (SEAs), 7 clear cell adenocarcinomas (CLAs), 7 endometrioid adenocarcinomas (ENAs), 4 mucinous adenocarcinomas (MUAs), 2 mucinous borderline tumors (MBTs), and 11 mucinous adenomas.
  
  
  RESULTS
  HIF-1 level (mg/ml) in the nucleus and HIF-1alpha level (mg/ml) in the cytoplasm were on average 0.116 and 0.178 for SEAs, 0.328 and 0.306 for CLAs, 0.171 and 0.305 for ENAs, 0.097 and 0.176 for MUAs, 0.224 and 0.180 for mucinous borderline tumors, 0.152 and 0.154 for mucinous adenomas. CLAs showed the highest levels for both of HIF-1 and HIF-1alpha, while MUAs showed the lowest levels of both. Mucinous adenomas were higher in HIF-1 than MUAs.
  
  
  CONCLUSIONS
  Hypoxic state was considered to be closely related to histological type of epithelial ovarian tumors, suggesting that CLAs may be most hypoxic. In the comparison of mucinous tumors, malignancies would not always become most hypoxic. Tumor size may not be strongly associated with hypoxic state.
authors.affiliation: Department of Pathology, Tokai University, Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyazawa
authors.forename: Masanori
authors.initials: M
authors.lastname: Yasuda
authors.forename: Mariko
authors.initials: M
authors.lastname: Fujita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirasawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kajiwara
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hirabayashi
authors.forename: Naoki
authors.initials: N
authors.lastname: Ogane
authors.forename: Michio
authors.initials: M
authors.lastname: Shimizu
authors.forename: Hideki
authors.initials: H
authors.lastname: Asanuma
authors.forename: Masaru
authors.initials: M
authors.lastname: Murakami
authors.forename: Susumu
authors.initials: S
authors.lastname: Takekoshi
authors.forename: Mikio
authors.initials: M
authors.lastname: Mikami
authors.forename: R Yoshiyuki
authors.initials: RY
authors.lastname: Osamura
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000236:Adenoma / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism; D002648:Child; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism*; D055815:Young Adult
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D004247:DNA